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Bioécologie

Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury

14 Mai 2015,

Publié par Bioécologie

Indicating Radiation Injury. Three Mile Island, Chernobyl, and Fukushima were catastrophic nuclear power plant accidents. The radiation from these accidents not only took an immediate toll on human lives, but will also persist long-term, as individuals will suffer from cancer, gut damage, and infections. On the cover, engineers at the Fukushima Daiichi Nuclear Power Plant fix the "ice wall" to reduce radiation-contaminated water from entering clean groundwater, and thus protect people from future radiation injury. In another effort to protect human health, Acharya et al. identified microRNAs associated with hematopoietic damage and long-term survival in mice exposed to different sublethal doses of total body irradiation. Such RNA signatures may distinguish humans with mild radiation-related injury from those with more severe (often nonrecoverable) bone marrow damage. Studies with human samples will allow for validation of such indicators, as well as investigation into new intervention measures, to improve patient care and to enhance survival after radiation exposure. [CREDIT: K. MAYAMA/EPA/CORBIS]
Indicating Radiation Injury. Three Mile Island, Chernobyl, and Fukushima were catastrophic nuclear power plant accidents. The radiation from these accidents not only took an immediate toll on human lives, but will also persist long-term, as individuals will suffer from cancer, gut damage, and infections. On the cover, engineers at the Fukushima Daiichi Nuclear Power Plant fix the "ice wall" to reduce radiation-contaminated water from entering clean groundwater, and thus protect people from future radiation injury. In another effort to protect human health, Acharya et al. identified microRNAs associated with hematopoietic damage and long-term survival in mice exposed to different sublethal doses of total body irradiation. Such RNA signatures may distinguish humans with mild radiation-related injury from those with more severe (often nonrecoverable) bone marrow damage. Studies with human samples will allow for validation of such indicators, as well as investigation into new intervention measures, to improve patient care and to enhance survival after radiation exposure. [CREDIT: K. MAYAMA/EPA/CORBIS]

S. S. Acharya, W. Fendler, J. Watson, A. Hamilton, Y. Pan, E. Gaudiano, P. Moskwa, P. Bhanja, S. Saha, C. Guha, K. Parmar, D. Chowdhury, Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury. Sci. Transl. Med. 7, 287ra69 (2015).

Abstract

Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation.

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